The major goals of these studies are to elucidate the individual roles of COX-1 and COX-2 in normal physiology and in various pathological states using the COX deficient mice. Included in these studies are the roles of the COX isoforms in gastric ulceration, lung inflammation, vascular development and blood pressure regulation. Additionally, effort within the laboratory has focused on using COX-1 and COX-2 deficient mouse ES cells to study the roles of COX-1 and COX-2 in endothelial cell development and angiogenesis. Studies suggest that neither the deficiency of COX-1 or COX-2 inhibited mouse ES cell differentiation into endothelial-like cells in vitro. Whereas studies with COX-1 and COX-2 selective inhibitors have indicated that the COX-2 inhibitors inhibits endothelial-like cell development by a COX independent mechanism.